energies available from the environment. So, for example, the intrinsic free energy difference between Z- and
B-forms is close to 2 kJ mol^1 for poly-d(GC) base pairs, only 1 kJ mol^1 for poly-d(Gm^5 C) base pairs, and
greater than 5 kJ mol^1 for poly-d(AT) base pairs. It thus appears that local structural fluctuations may be key
elements in the mediation of biological regulatory functions through the B–Z transition.68,69
2.5.4 Rapid DNA Motions
Rotations of single bonds, either alone or in combination, are responsible for a range of very rapid DNA
motions with time scales down to fractions of a nanosecond. For example, the twisting of base pairs
around the helix axis has a life time around 10–8s while crankshaft rotations of the , , and C-O-P-
O-C bonds (see Figure 2.11) lead to an oscillation in the position of the phosphorus atoms on a millisecond
time scale. Various calculations on the inter-conversion of C3-endoand C2-endosugar pucker have
given low activation energy barriers for their inter-conversion, in the range 3–20 kJ mol^1 , showing that
the conformers are in rapid, although weighted, equilibrium at 37°C. Lastly, rapid fluctuations in propeller
twist can result from oscillations of the glycosylic bond.
2.6 Higher-Order DNA Structures
The way in which eukaryotic DNA is packaged in the cell nucleus is one of the wonders of the macro-
molecular structure. In general, higher organisms have more DNA than lower ones (Table 2.10) and this
calls for correspondingly greater condensation of the double helix. Human cells contain a total of
7.8 109 bp, which corresponds to an extended length of about 2 m. The DNA is packed into 46 cylin-
drical chromosomes of total length 200 m, which gives a net packaging ratio of about 10^4 for such
metaphase human chromosomes (see also Section 6.4). The overall process has been broken down into
two stages: the formation of nucleosomes and the condensation of nucleosomes into chromatin.^70
2.6.1 Nucleosome Structure
The first stage in the condensation of DNA is the nucleosome, whose core has been crystallised by Aaron
Klug and John Finch and analysed using X-ray diffraction. The DNA duplex is wrapped around a block of
eight histone proteins to give 1.75 turns of a left-handed superhelix (Section 10.6, Figure 10.15).71,72This
process achieves a packing ratio of 7. The number of base pairs involved in nucleosome structures varies
from species to species, being 165 bp for yeast, 183 bp for HeLa cells, 196 bp for rat liver and 241 bp for
sea urchin sperm. Such nucleosomes are joined by linker DNA whose length ranges from 0 bp in neurons
to 80 bp in sea urchin sperm but usually averages 30–40 bp. The details of packaging the histone proteins
are discussed later (Section 10.6.1).^73
68 Chapter 2
Table 2.10 Cellular DNA content of various species
Organism Numbers of base pairs DNA length (mm) Number of chromosomes
Escherichia coli 4 106 1.4 1
Yeast
(Saccharomyces cerevisiae) 1.4 106 4. 61 6
Fruit fly
(Drosophila melanogaster) 1.7 107 56.0 4
Humans
(Homo sapiens) 3.9 109 990.0 23Note: Values are provided for haploid genomes.